DESCRIPTION: The long-term goal of the work described is to understand how extracellular signals orchestrate changes in the Schwann cell phenotype. The main hypothesis to be tested is that the Ras/MAP kinase pathway acting through transcription factors AP-2 and C/EBP increases myelin P0 expression and the extracellular signal that triggers this pathway is laminin, a component of basal lamina. The aims of this proposal are to investigate whether MAP kinase and cAMP activation of myelin genes occur through these two transcription factors and to demonstrate that laminin induction of myelin genes utilizes the ras pathway. An understanding of the mechanism whereby the Schwann cell phenotype is regulated can allow for experimental manipulation of this cell which might be helpful in several medical areas such as designing therapies for demyelinating diseases and transplantation for spinal cord regeneration.